Background The efficacy of mepolizumab is well documented in severe eosinophilic asthma (SEA), although the stringent selection criteria adopted by SEA clinical trials limits the generalizability of results. Objective Our study evaluated the effectiveness and safety of mepolizumab in patients with SEA in Spain. The primary efficacy endpoint was the change in the rate of clinically significant asthma exacerbations 12 months after starting mepolizumab compared to the baseline rate in the 12 months prior to treatment. Patients were stratified by baseline blood eosinophil counts. Methods We conducted a multicentric observational cohort study of SEA patients treated with mepolizumab across 24 specialized hospital asthma units in Spain. Severe exacerbation rate, lung function, oral corticosteroid use (OCS) and asthma control test (ACT) were retrospectively collected and compared during the 12-month pre- and post-mepolizumab treatment. Adverse events were also investigated. Results A total of 318 patients with SEA were included (mean age: 56.6 years, 69.2% female). Exacerbation rates decreased by 77.5%, and 50.6% of patients did not suffer any exacerbations during the 12 months of treatment. The difference in forced expiratory volume in 1 s (FEV1) pre- and post-bronchodilator after starting mepolizumab was 0.21 (0.46) L (95% CI 0.14–0.27) (p < 0.001). Exacerbations and lung function significantly improved across all eosinophil subgroups. Among the 98 patients on OCS, 47.8% were able to discontinue this treatment and the mean daily dose was decreased by 59.9%. The baseline ACT score was 14.1, increasing by a mean (SD) of 6.7 points (1.9) at 12 months. Adverse events related to mepolizumab were uncommon. Conclusions This real-world study of SEA patients confirms that mepolizumab is effective in reducing clinically meaningful exacerbations, improving lung function, and decreasing OCS dependence and mean OCS dose at 12 months, irrespective of baseline eosinophil counts.

Asthma is characterised by chronic airway inflammation, airway obstruction and hyper-responsiveness. The inflammatory cascade in asthma comprises a complex interplay of genetic factors, the airway epithelium, and dysregulation of the immune response. Prostaglandin D2 (PGD2) is a lipid mediator, predominantly released from mast cells, but also by other immune cells such as TH2 cells and dendritic cells, which plays a significant role in the pathophysiology of asthma. PGD2 mainly exerts its biological functions via two G-protein-coupled receptors, the PGD2 receptor 1 (DP1) and 2 (DP2). The DP2 receptor is mainly expressed by the key cells involved in type 2 immune responses, including TH2 cells, type 2 innate lymphoid cells and eosinophils. The DP2 receptor pathway is a novel and important therapeutic target for asthma, because increased PGD2 production induces significant inflammatory cell chemotaxis and degranulation via its interaction with the DP2 receptor. This interaction has serious consequences in the pulmonary milieu, including the release of pro-inflammatory cytokines and harmful cationic proteases, leading to tissue remodelling, mucus production, structural damage, and compromised lung function. This review will discuss the importance of the DP2 receptor pathway and the current understanding of its role in asthma.

Asthma is an airway disease characterised by chronic inflammation with intermittent or permanent symptoms including wheezing, shortness of breath, chest tightness, and cough, which vary in terms of their occurrence, frequency, and intensity. The most common associated feature in the airways of patients with asthma is airway inflammation. In recent decades, efforts have been made to characterise the heterogeneous clinical nature of asthma. The interest in improving the definitions of asthma phenotypes and endotypes is growing, although these classifications do not always correlate with prognosis nor are always appropriate therapeutic approaches. Attempts have been made to identify the most relevant molecular and cellular biomarkers underlying the immunopathophysiological mechanisms of the disease. For almost 50 years, immunoglobulin E (IgE) has been identified as a central factor in allergic asthma, due to its allergen-specific nature. Many of the mechanisms of the inflammatory cascade underlying allergic asthma have already been elucidated, and IgE has been shown to play a fundamental role in the triggering, development, and chronicity of the inflammatory responses within the disease. Blocking IgE with monoclonal antibodies such as omalizumab have demonstrated their efficacy, effectiveness, and safety in treating allergic asthma. A better understanding of the multiple contributions of IgE to the inflammatory continuum of asthma could contribute to the development of novel therapeutic strategies for the disease.

(2011). Omalizumab in the management of oral corticosteroid-dependent IGE-mediated asthma patients. Current Medical Research and Opinion: Vol. 27, No. 1, pp. 45-53. doi: 10.1185/03007995.2010.536208

Purpose. To establish the prevalence of bronchiectasis in asthma in relation to patients’ oral corticosteroid requirements and to explore whether the increased risk is due to blood immunoglobulin (Ig) concentration.Methods. Case-control cross-sectional study, including 100 sex- and age-matched patients, 50 with non-steroid-dependent asthma (NSDA) and 50 with steroid-dependent asthma (SDA). Study protocol: (a) measurement of Ig and gG subclass concentration; (b) forced spirometry; and (c) high-resolution thoracic computed tomography. When bronchiectasis was detected, a specific etiological protocol was applied to establish its etiology.Results. The overall prevalence of bronchiectasis was 12/50 in the SDA group and 6/50 in the NSDA group (p=ns). The etiology was documented in six patients (four NSDA and two SDA). After excluding these patients, the prevalence of bronchiectasis was 20% (10/50) in the SDA group and 2/50 (4%) in the NSDA group (P<0.05). Patients with asthma-associated bronchiectasis presented lower FEV₁values than patients without bronchiectasis, but the levels of Ig and subclasses of IgG did not present differences.Conclusions. Steroid-dependent asthma seems to be associated with a greater risk of developing bronchiectasis than non-steroid-dependent asthma. This is probably due to the disease itself rather than to other influencing factors such as immunoglobulin levels.